This project proposes to test the hypothesis that synaptic plasticity at the neuromuscular junction (NMJ) involves alterations in proteins present within the matrix of the junction itself. The basal lamina (BL) or basement membrane (BM) of the muscle fiber fills the cleft of the NMJ and has been identified with such roles as underlying adhesion of nerve and muscle membranes, induction of nerve terminal differentiation in regeneration of nerve-muscle connections, clustering of acetylcholine receptors and anchoring of junctional acetylcholinesterase (AchE). The major proteins of this NMJ-BL are thought to be AchE, fibronectin, laminin and type IV collagen plus several others. The hypothesis states that these are regulated in a coordinated manner and at least partly depend on innervation. Neurotrophic influence may be negative inhibiting release of proteolytic enzymes from muscle. It may be positive, initially favoring the release, and once innervation occurs regulated graded release. The released proteases are thought to be neutral and extracellular and probably collagenase(s), "gelatinases", elastase and/or plasminogen activators. Denervation experiments in vivo, tissue and organ culture models will be used to test this hypothesis during the grant period. Success in this project should shed light on changes which occur in the development, aging and neuromuscular diseases of man.